Wnt-modified materials mediate asymmetric stem cell division to direct human osteogenic tissue formation for bone repair

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42 Citations (Scopus)

Abstract

The maintenance of human skeletal stem cells (hSSCs) and their progeny in bone defects is a major challenge. Here, we report on a transplantable bandage containing a three-dimensional Wnt-induced osteogenic tissue model (WIOTM). This bandage facilitates the long-term viability of hSSCs (8 weeks) and their progeny, and enables bone repair in an in vivo mouse model of critical-sized calvarial defects. The newly forming bone is structurally comparable to mature cortical bone and consists of human and murine cells. Furthermore, we show that the mechanism of WIOTM formation is governed by Wnt-mediated asymmetric cell division of hSSCs. Covalently immobilizing Wnts onto synthetic materials can polarize single dividing hSSCs, orient the spindle and simultaneously generate a Wnt-proximal hSSC and a differentiation-prone Wnt-distal cell. Our results provide insight into the regulation of human osteogenesis and represent a promising approach to deliver human osteogenic constructs that can survive in vivo and contribute to bone repair.
Original languageEnglish
Pages (from-to)108-118
Number of pages11
JournalNATURE MATERIALS
Volume20
Issue number1
Early online date21 Sept 2020
DOIs
Publication statusPublished - 1 Jan 2021

Keywords

  • cell delivery
  • Biomaterials
  • mesenchymal stem cell
  • Mesenchymal Stem Cell Transplantation
  • Tissue engineering

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